Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jingwu Road 324, Jinan, 250021, Shandong, China.
Department of Orthopedics, Linyi People's Hospital Affiliated to Shandong University, Linyi, 276003, Shandong, China.
Cell Biol Int. 2018 May;42(5):580-588. doi: 10.1002/cbin.10934. Epub 2018 Feb 23.
Osteosarcoma represents the most common primary malignant bone tumor in children and adolescents, which shows severe resistance toward standard chemotherapy because of high invasive capacity and growing incidence. Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors. However, little information about SeC-induced growth inhibition against human osteosarcoma is available. Herein, the anticancer efficiency and underlying mechanism of SeC against human osteosarcoma were evaluated in vitro and in vivo. The results revealed that SeC significantly inhibited MG-63 human osteosarcoma cells growth in vitro through induction of S-phase arrest and apoptosis, as reflected by the decrease of cyclin A and CDK-2, PARP cleavage, and caspases activation. SeC treatment also resulted in mitochondrial dysfunction through affecting Bcl-2 family expression. Moreover, SeC triggered p53 phosphorylation by inducing reactive oxygen species (ROS) overproduction. ROS inhibition effectively blocked SeC-induced cytotoxicity and p53 phosphorylation. Importantly, MG-63 human osteosarcoma xenograft growth in nude mice was significantly suppressed in vivo through triggering apoptosis and p53 phosphorylation. These results indicated that SeC had the potential to inhibit human osteosarcoma cells growth in vitro and in vivo through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation, which validated the potential application of Se-containing compounds in treatment of human osteosarcoma.
骨肉瘤是儿童和青少年中最常见的原发性恶性骨肿瘤，由于其侵袭能力强、发病率不断上升，对标准化疗具有严重的耐药性。硒代半胱氨酸（SeC）是一种天然存在的含硒氨基酸，对多种人类肿瘤具有极好的抗癌活性。然而，关于 SeC 诱导的人类骨肉瘤生长抑制的信息很少。本文在体外和体内评估了 SeC 对人类骨肉瘤的抗癌效率和作用机制。结果表明，SeC 通过诱导 S 期阻滞和细胞凋亡，显著抑制了体外 MG-63 人骨肉瘤细胞的生长，这反映在细胞周期蛋白 A 和 CDK-2 的减少、PARP 裂解和半胱天冬酶的激活。SeC 处理还通过影响 Bcl-2 家族的表达导致线粒体功能障碍。此外，SeC 通过诱导活性氧（ROS）的过度产生触发 p53 磷酸化。ROS 抑制有效地阻断了 SeC 诱导的细胞毒性和 p53 磷酸化。重要的是，通过触发细胞凋亡和 p53 磷酸化，SeC 显著抑制了裸鼠体内 MG-63 人骨肉瘤异种移植物的生长。这些结果表明，SeC 通过触发线粒体功能障碍和 ROS 介导的 p53 磷酸化，具有抑制体外和体内人类骨肉瘤细胞生长的潜力，验证了含硒化合物在治疗人类骨肉瘤中的应用潜力。
